The long-term objectives of this proposal are: a) to characterize the electrical membrane properties and morphology of lamina I neurons in the subnucleus caudalis of the trigeminal sensory nuclear complex, b) to determine the synaptic responses of these neurons to activation of trigeminal afferent inputs, c) to examine how selective interference with inhibitory neurotransmitter receptors alters the synaptic responses of lamina I neurons. To achieve these objectives, various intracellular recording and histochemical techniques will be used to study the membrane properties, synaptic responses and morphology of trigeminal neurons in the horizontal slice preparation of the guinea pig brainstem. Hypotheses to be tested include: 1) high frequency stimulation of trigeminal afferents produces slow, neuropeptide-mediated excitatory potentials in subnucleus caudalis lamina I neurons 2) the substance P-mediated slow excitatory potentials are evoked via the NK1 tachykinin receptor subtype 3) paroxysmal discharges may be evoked in lamina I neurons following blockade of the GABA(Beta)-receptor subtype. The proposed studies will serve as a basis for the in depth analysis of signal transmission in the trigeminal system. The obtained knowledge can subsequently be used to provide a scientific basis for the complete understanding and treatment of debilitating conditions such as myofacial pain and trigeminal neuralgia which are of major clinical significance in dentistry.